Title:HIV Associated Neurodegenerative Disorders: A New Perspective on the Role of Lipid Rafts in Gp120-Mediated Neurotoxicity
VOLUME: 16 ISSUE: 4
Author(s):Lisa K. Smith, Thomas B. Kuhn*, Jack Chen and James R. Bamburg
Affiliation:Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, AK, Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks, AK, Department of Biology and Wildlife, Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK, Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO
Keywords:gp120, neurodegeneration, lipid raft, actin-cofilin rod, cholesterol, neuron, CNS.
Abstract:The implementation of combination antiretroviral therapy (cART) as the primary means
of treatment for HIV infection has achieved a dramatic decline in deaths attributed to AIDS and the
reduced incidence of severe forms of HIV-associated neurocognitive disorders (HAND) in infected
individuals. Despite these advances, milder forms of HAND persist and prevalence of these forms of
neurocognitive impairment are rising with the aging population of HIV infected individuals. HIV
enters the CNS early in the pathophysiology establishing persistent infection in resident macrophages
and glial cells. These infected cells, in turn, secrete neurotoxic viral proteins, inflammatory
cytokines, and small metabolites thought to contribute to neurodegenerative processes. The viral envelope
protein gp120 has been identified as a potent neurotoxin affecting neurodegeneration via indirect
and direct mechanisms involving interactions with chemokine co-receptors CCR5 and
CXCR4. This short review focuses on gp120 neurotropism and associated mechanisms of neurotoxicity
linked to chemokine receptors CCR5 and CXCR4 with a new perspective on plasma membrane
lipid rafts as an active participant in gp120-mediated neurodegeneration underlying HIV induced
CNS pathology.
